Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

The HIV-1 rev trans-activator acts through a structured target sequence to activate nuclear export of unspliced viral mRNA

Abstract

HUMAN immunodeficiency virus type 1 (HIV-1) replication requires the expression of two classes of viral mRNA. The early class of HIV-1 transcripts is fully spliced and encodes viral regulatory gene products. The functional expression of one of these nuclear regulatory proteins, termed Rev (formerly Art or Trs), induces the cytoplasmic expression of the incompletely spliced, late class of HIV-1 mRNAs that encode the viral structural proteins, including Gag and Env1–6. Here, we provide evidence that this induction reflects the export from the cell nucleus to the cytoplasm of a pool of unspliced viral RNA constitutively expressed in the nucleus. The hypothesis that Rev acts on RNA transport, rather than splicing, is further supported by the observation that the cytoplasmic expression of a non-spliceable HIV-1 env gene sequence is also subject to Rev regulation. Here we show that this Rev response requires a specific target sequence which coincides with a complex RNA secondary structure present in the env gene. The response to Rev is fully maintained when this sequence is relocated to other exonic or intronic locations within env but is ablated by inversion. These results indicate that the HIV-1 rev gene product induces HIV-1 structural gene expression by activating the sequence-specific nuclear export of incompletely spliced HIV-1 RNA species.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Feinberg, M. B., Jarrett, R. F., Aldovini, A., Gallo, R. C. & Wong-Staal, F. Cell 46, 807–817 (1986).

    Article  CAS  Google Scholar 

  2. Sodroski, J. et al. Nature 321, 412–517 (1986).

    Article  ADS  CAS  Google Scholar 

  3. Knight, D. M., Flomerfelt, F. A. & Ghrayeb, J. Science 236, 837–840 (1987).

    Article  ADS  CAS  Google Scholar 

  4. Terwilliger, E. et al. J. Virol. 62, 655–658 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Sadaie, M. R., Benter, T. & Wong-Staal, F. Science 239, 910–914 (1988).

    Article  ADS  CAS  Google Scholar 

  6. Malim, M. H., Hauber, J., Fenrick, R. & Cullen, B. R. Nature 335, 181–183 (1988).

    Article  ADS  CAS  Google Scholar 

  7. Gutman, D. & Goldenberg, C. J. Science 241, 1492–1495 (1988).

    Article  ADS  CAS  Google Scholar 

  8. Cullen, B. R. Cell 46, 973–982 (1986).

    Article  CAS  Google Scholar 

  9. Le, S.-Y., Chen, H.-H., Braun, M. J., Gonda, M. A. & Maizel, J. V. Nucleic Acids Res. 16, 5153–5168 (1988).

    Article  CAS  Google Scholar 

  10. Muesing, M. A., Smith, D. H. & Capon, D. J. Cell 48, 691–701 (1987).

    Article  CAS  Google Scholar 

  11. Feng, S. & Holland, E. C. Nature 334, 165–167 (1988).

    Article  ADS  CAS  Google Scholar 

  12. Katz, R. A., Kotler, M. & Skalka, A. M. J. Virol. 62, 2686–2695 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Arrigo, S. & Beemon, K. Molec. Cell Biol. 8, 4858–4867 (1988).

    Article  CAS  Google Scholar 

  14. Rosen, C. A., Terwilliger, E., Dayton, A., Sodroski, J. G. & Haseltine, W. A. Proc. natn. Acad. Sci. U.S.A. 85, 2071–2075 (1988).

    Article  ADS  CAS  Google Scholar 

  15. Nevins, J. R. A. Rev. Biochem. 52, 441–466 (1983).

    Article  CAS  Google Scholar 

  16. Darnell, J. E. Prog. Nucleic Acid Res. Molec. Biol. 19, 493–511 (1976).

    Article  CAS  Google Scholar 

  17. Buchman, A. R. & Berg, P. Molec. cell. Biol. 8, 4395–4405 (1988).

    Article  CAS  Google Scholar 

  18. Ratner, L. et al. Nature 313, 277–284 (1985).

    Article  ADS  CAS  Google Scholar 

  19. Salser, W. Cold Spring Harb. Symp. quant. Biol. 42, 993–1004 (1977).

    Google Scholar 

  20. Cech, T. R. et al., Proc. natn. Acad. Sci. U.S.A. 80, 3903–3907 (1983).

    Article  ADS  CAS  Google Scholar 

  21. Greenberg, M. E. & Ziff, E. B. Nature 311, 433–438 (1984).

    Article  ADS  CAS  Google Scholar 

  22. Chirgwin, J. M., Przybyla, A. E., MacDonald, R. J. & Rutter, W. J. Biochemistry 18, 5294–5304 (1979).

    Article  CAS  Google Scholar 

  23. Thomas, P. S. Proc. natn. Acad. Sci. U.S.A. 77, 5201–5205 (1980).

    Article  ADS  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Malim, M., Hauber, J., Le, SY. et al. The HIV-1 rev trans-activator acts through a structured target sequence to activate nuclear export of unspliced viral mRNA. Nature 338, 254–257 (1989). https://doi.org/10.1038/338254a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/338254a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing